The ultimate objective of this research is to describe the pathogenesis of the biological consequences of inhalation of mineral particles into the lungs which occurs under a variety of occupational and environmental circumstances. Previous investigations have shown that exposure of primary macrophage cultures to toxic mineral particles such as silica or asbestos results in rapid injury and cell death. These acute cytotoxic reactions of macrophages to toxic mineral particles may initiate a series of events which culminates in pulmonary fibrosis and cancer. This proposed research will study the pathogenesis of silica cytotoxicity to mouse macrophage tumor cells P388D1 in vitro. In this model system, various structural and functional events will be evaluated as being causally related to the production of silica cytotoxicity. The objectives of the proposed experiments are: 1) to detemine what agents are able to delay or prevent cytotoxicity in P388D1 cells exposed to silica and 2) to measure specific biochemical changes in P388D1 cells exposed to silica. The specific changes to be studied are lysosomal enzyme release, degradation of cellular macromolecules, cell membrane function, and specific intracellular enzyme activities.